study of the safety and efficacy of sti-6643 in subjects with advanced solid tumors

Conditions: Solid Tumor; Relapsed Solid Neoplasm; Refractory Tumor

Summary: this is a first-in-human, phase 1, open-label, dose-escalation study of sti-6643 administered by intravenous infusion in subjects with a relapsed/refractory advanced solid tumor.

this is a first-in-human, phase 1, open-label, dose-escalation study of sti-6643 administered by intravenous infusion in subjects with a relapsed/refractory advanced solid tumor. the study will determine an mtd and rp2d using a conventional 3+3 study design with priming dose identification (pdi) stage and therapeutic dose (td) escalation (tde) stage. dose limiting toxicity evaluated over the initial 28 days of sti-6643 administration.

Eligibility criteria:
inclusion criteria: * signed informed consent * age ≥ 18 years * ecog performance status ≤ 2 * histologically- or cytologically-confirmed solid tumor * patient has relapsed, is refractory to, or intolerant of standard of care therapy * no available approved therapy that may provide clinical benefit (per investigator) * measurable or evaluable disease by recistv1.14 * life expectancy of \> 12 weeks (per investigator) * adequate laboratory parameters including: 1. absolute neutrophil count (anc) ≥ 1500/mm3 2. platelets ≥ 100,000/mm3 3. hemoglobin ≥ 12 g/dl (in the absence of transfusion over the prior 2 weeks) 4. ast/sgot ≤ 2.5 x uln (≤ 5 x uln if known liver involvement) 5. alt/sgpt ≤ 2.5 x uln (≤ 5 x uln if known liver involvement) 6. total bilirubin ≤ 2.0 x uln (unless diagnosis of gilbert's syndrome in which case \< 3.0 times uln) 7. serum creatinine ≤ 2.0 x uln or estimated gfr ≥ 45 ml/min (per cockcroft- gault equation) * if residual treatment related toxicity from prior therapy: 1. treatment related toxicity resolved to ≤ grade 1 (alopecia excepted), or 2. treatment related toxicity resolved to ≤ grade 2 with prior approval of the medical monitor * willingness to comply with the study schedule and all study requirements * \[females\] must be postmenopausal, surgically sterile, or agree to use adequate contraception (per investigator) throughout the study and for a least 30 days following the last dose * \[males\] must be surgically sterile or must agree to use adequate contraception (per investigator) throughout the study and for at least 30 days following the last dose * \[males\] willingness to refrain from donating sperm throughout the study and for at least 30 days following the last dose * \[females\] if of child-bearing potential, must have a negative serum pregnancy test exclusion criteria: * participating in any other interventional clinical study * previous exposure to an anti-cd47 or sirpα antibody * ≤ 28 days (or 5 half-lives if shorter) between of systemic anti-tumor treatment (e.g., chemotherapy, endocrine therapy, immunotherapy, cellular therapy) and the 1st dose of sti-6643 * ≤ 28 days from prior irradiation (≤ 7 days from limited field irradiation for control of symptoms) and the 1st dose of sti-6643 * ≤ 28 days between major surgery (≤ 7 days from minor surgical procedures, no waiting period following central catheter placement) * ≤ 7 days between administration of g-csf, gm-csf, erythropoietin, thrombopoietin or il11 and the 1st dose of sti-6643 * ≤ 7 days between systemic immunosuppressive therapy in excess of 10 mg/day prednisone equivalent and the 1st dose of sti-6643 (topical or inhaled corticosteroids not restricted) * ≤ 28 days between a live attenuated vaccine and the 1st dose of sti-6643 * known central nervous system (cns) involvement with tumor (e.g., metastases, meningeal carcinomatosis) * active second malignancy requiring ongoing systemic treatment * history of primary immunodeficiency disorders * history of active pulmonary tuberculosis * history of covid-19 symptoms unless covid-19 test negative ≤ 72 hours of the 1st dose of sti-6643 * ≤ 12 weeks from an allogeneic hematopoietic stem cell transplant and c1d1 or active graft-versus-host disease (gvhd) * active infection (e.g., bacterial, viral, fungal) requiring systemic treatment ≤ 72 hours of the 1st dose of sti-6643 * known hiv-positive with cd4+ cell counts \< 350 cells/ul or a history of an aids defining opportunistic infection * known t-cell leukemia virus type 1 (htlv1) infection, hepatitis b virus (hbv) or hepatitis c virus (hcv) viremia * significant risk for hbv reactivation (defined as hbsag positive, hbcab positive or hbv dna positive) * detectable hcv rna * pregnant or breast feeding * history of clinically significant cardiovascular abnormalities including: 1. congestive heart failure (nyha classification ≥ 3) within 6 months of the 1st dose of sti-6643 2. unstable angina pectoris 3. ≤ 6 months from myocardial infarction and the 1st dose of sti-6643 4. arrhythmias (other than atrial fibrillation) requiring ongoing treatment 5. qtcf interval \> 480 msec (using fridericia's formula) 6. uncontrolled hypertension (i.e., systolic bp \> 180 mmhg or diastolic bp \> 100 * any condition, including the presence of laboratory abnormalities, that places the subject at an unacceptable risk if the subject was to participate in the study.

Keywords: solid tumor